New shop kamagra australia online viagradirect.net with a lot of generic and brand medicament with cheap price and fast delivery.

The promotion of olanzapine in primary care: an examination of internal industry documents

Social Science & Medicine 69 (2009) 14–20
The promotion of olanzapine in primary care: An examination of internal industrydocuments
Department of Psychology, Metropolitan State University, 1450 Energy Park Drive, St. Paul, MN 55108, United States
Media reports have discussed how olanzapine was marketed off-label for dementia and subsyndromal
bipolar disorder. Much of this marketing occurred in primary care settings. However, these reports haveprovided few details. In legal proceedings, Lilly disclosed internal documents that detail the strategies
utilized to market olanzapine. The current paper addresses the marketing of olanzapine in detail based
upon a review of these documents. All 358 documents released by Lilly are publicly available online.
Documents were utilized for this review if they were relevant to the marketing of olanzapine in primary
care settings in the United States. It was found that olanzapine was marketed off-label in primary care
settings for relatively mild symptoms that were framed as bipolar disorder and schizophrenia. A key
strategy in this campaign was the use of hypothetical patient proﬁles in detailing visits, most of which
clearly failed to meet diagnostic criteria for any recognized mental disorder. Evidence emerged that
olanzapine was also marketed off-label as a treatment for dementia.
Ó 2009 Elsevier Ltd. All rights reserved.
Olanzapine (ZyprexaÒ) is an atypical antipsychotic agent
including a criminal ﬁne of $515 million, subject to the guilty
that is currently Federal Drug Administration (FDA)-approved for
plea being accepted by the U.S. District Court. This is the
the acute and long-term treatment of bipolar I disorder and
largest individual corporate criminal ﬁne in US history
schizophrenia as well as agitation associated with these condi-
tions. A media report alleged that olanzapine was promoted off-
tive ofﬁcer of Lilly, said in a press release that ‘‘we deeply regret
label as a treatment for dementia and that sales representatives
the past actions covered by this misdemeanor plea’’
were instructed to market olanzapine as a treatment for symptoms
In October 2008, Lilly also settled olanzapine marketing-
of schizophrenia and bipolar disorder, even if patients did not
related claims brought by 33 states for $62 million (
necessarily meet the full diagnostic criteria for either condition
(). Likewise, there has been further discussion of
Olanzapine use has been linked to signiﬁcant weight gain
the off-label marketing of olanzapine for dementia ).
Reports have suggested that off-label marketing of olanzapine
occurred in primary care settings ). Lilly originally
denied allegations of off-label marketing (
but in January 2009, as part of a global settlement
with the United States to resolve criminal and civil allegations that
have led to serious health consequences. It is certainly possible
it promoted Zyprexa for uses not approved by the FDA, Lilly agreed
that some patients taking olanzapine for an off-label condition
to plead guilty to a misdemeanor criminal charge of misbranding
received some symptomatic relief. However, a meta-analysis indi-
cated that olanzapine showed no beneﬁt versus placebo in treating
speciﬁcally admitted that between September 1999 and 31 March
2001 it promoted Zyprexa in elderly populations as treatment for
At present, there is no evidence from controlled clinical trials
dementia, including Alzheimer’s dementia. Furthermore, the
available regarding the efﬁcacy of olanzapine in treating relatively
company has agreed to a monetary settlement of $1.415 billion,
mild nervous symptoms such as those for which olanzapine wasmarketed.
While reports have described various details of marketing
* Tel.: þ1 651 999 5826; fax: þ1 651 999 5822.
in-depth analysis of the topic has not appeared in the media and no
0277-9536/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.doi:10.1016/j.socscimed.2009.05.001
G.I. Spielmans / Social Science & Medicine 69 (2009) 14–20
peer-reviewed article has addressed the latest revelations
surrounding olanzapine’s marketing. This paper presents ﬁndingsfrom internal Lilly documents which were disclosed by Lilly in legal
proceedings but which are now publicly available online. The paperwill describe Lilly’s high expectations for olanzapine and how
Lilly clearly had high sales expectations for olanzapine.
olanzapine was marketed in primary care using broadened deﬁni-
According to a 1997 document, olanzapine ‘‘is a profound corporate
tions of bipolar disorder and schizophrenia. In addition, evidence
opportunity’’ and was intended to be ‘‘the world’s number one
will be discussed regarding the marketing of olanzapine as
neuroscience pharmaceutical in history’’ In 2001,
a treatment for both dementia and ‘‘schizophrenia lite,’’ as will
a document describing a Zyprexa Product Team meeting stated,
details of the main methods used to market the drug, primarily
‘‘The company is betting the farm on Zyprexa.the ability of Eli Lilly
focusing on the promotion of olanzapine to primary care
to remain independent.depends solely on our ability to achieve
world class commercialization of Zyprexa [emphases in original].’’The same document stated, ‘‘If we succeed, Zyprexa will be themost successful pharmaceutical product ever.we will have made
history’’ (Olanzapine sales were expected to reach$6 billion by 2006 and nearly $8 billion by 2010 ).
Indeed, sales have been robust, with global olanzapine salesranking among the top eight drugs in sales each year from 2000to
Documents pertaining to Lilly’s marketing of olanzapine as
2007, ranking fourth among all drugs in 2002 (, pg. 9)
well as side effects of the medication were obtained via subpoena,
at about $4 billion, and leveling off at about $4.7–$5.0 billion
and were expected to remain under seal. However, the documents
were leaked to a New York Times reporter (Alex Berenson), who
). In order to help reach these impressive sales
wrote several pieces based upon the documents (
goals, olanzapine was marketed not only toward psychiatrists but
there has been controversy surrounding the disclosure of the
), an effort that met with some success. Though constituting
documents outside the litigation (), the US District
a relatively small fraction of overall sales, it was estimated in 2002
Court refused to grant injunctions to prevent ﬁve named websites
that olanzapine sales in primary care would total about $368
from publishing the documents. Furthermore, the judge in the
million in 2003 (pg. 6). Further sales ﬁgures for
case stated that ‘‘no website is enjoined from disseminating
olanzapine in primary care were unavailable from the documents.
As early as 1995 (, pg. 43), Lilly discussed seeking
approval for olanzapine as a treatment for bipolar disorder. Shortlyafter its March 2000 FDA approval as a short-term treatment for
The entire set of documents was reviewed by the present
bipolar disorder, Lilly began a promotional initiative, dubbed Viva
author. The majority of the documents were related to health
Zyprexa later retitled Zyprexa Limitless (
concerns, particularly hyperglycemia and/or diabetes. Of the 358
) that aimed to increase the use of olanzapine in primary care
documents, 67 were relevant to the present focus on marketing in
settings. About 59,000 primary care physicians (PCPs) in the US
primary care and these are the focus of this paper (of the remainder,
were labeled as ‘‘key targets’’ of this program, which launched in
50 related to marketing, but focused on health concerns rather than
approximately October 2000 pg. 1). According to
primary care, and the remaining 241 documents were unrelated to
the brand manager for Zyprexa, Mike Bandick, ‘‘[olanzapine’s]
marketing). Documents ranged in dates from 1995 to 2004 and
potential in this arena is virtually untapped’’ (pg. 1). In multiple
included a variety of memoranda, reports, email messages, and
documents, the marketing message for olanzapine in primary care
was stated clearly: ‘‘Zyprexa: The safe, proven solution in mood,thought, and behavior disorders’’ , pg. 1; , pg. 6). Additionally, the marketing strategy was designed to
‘‘ﬁt within the brand vision of broad spectrum efﬁcacy’’ pg. 1), though olanzapine was only FDA-approved for the
The documents were reviewed using the principles of grounded
treatment of bipolar manic and mixed episodes and for schizo-
theory in which no a priori hypothesis was tested; rather, obser-
phrenia when the primary care marketing campaign began. Ban-
vations were made and theory generated from the obtained
dick further stated that the intention of Viva Zyprexa was to
‘‘redeﬁne the way PCPs treat mood, thought, and behavioral
consistent in their portrayal of tactics used to market olanzapine in
disturbances’’ (pg. 12) and another document
primary care settings. As each document relevant to marketing in
stated that a main component of the primary care marketing
primary care was reviewed, the author compiled notes about the
message was to ‘‘focus on symptoms and behaviors found in mood,
key points contained within the document. These notes were
thought, and behavioral disturbances’’ , pg. 9,
grouped into several different categories (primary care, marketing,
emphasis in original). In a similar vein, olanzapine was rebranded
dementia, bipolar, etc.). After review of the initial set of notes, the
as a ‘‘broad spectrum psychotropic’’ in the primary care campaign
author compiled a more abbreviated set of notes and checked the
original documents to ensure they were cited accurately. From both
The promotion of olanzapine in primary care was associated
sets of notes and the set of accompanying documents, the current
with some concerns at Lilly, including that ‘‘Zyprexa’s primary
paper was compiled. The author maintains full responsibility for
indications – schizophrenia and bipolar – are not viewed as PCP-
the data extraction and interpretation of the referenced internal
treated conditions, so there’s not a speciﬁc indication for Lilly reps
to promote in the PCP segment’’ and that most PCPs write very few
G.I. Spielmans / Social Science & Medicine 69 (2009) 14–20
antipsychotic and mood stabilizer prescriptions (
pg. 1). The promotion of Zyprexa in the primary care settingincluded the use of hypothetical patient proﬁles as well as posi-
Olanzapine was marketed in the primary care setting based
tioning olanzapine ‘‘as the next incremental step in the PCP’s
largely upon the presentation of scripted patient proﬁles
expanding clinical orbit: e.g., SSRI’s /2nd generation [antide-
). A total of 10 different proﬁles were discussed in the
pressants] / safe gentle psychotropics’’ (, pg. 1).
obtained documents. The majority of these patients fall into the
Using a similar analogy, it was stated: ‘‘just as Prozac revolutionized
bipolar spectrum, deﬁned quite loosely.
the treatment of depression in the late 80s and throughout the 90s,
A hypothetical patient named Donna was featured in a handful
so too will Zyprexa forever change the way primary care physicians
view and treat bipolar disorder’’ pg. 3).
). The ‘‘goal and focus [was] on creating a market [for
It was clear that olanzapine was not to be marketed in primary
olanzapine]’’ with her case pg. 2). She was
care as a treatment for severe bipolar disorder (bipolar I), as these
described as ‘‘a single mom in her mid-30s, appearing in your ofﬁce
patients are generally referred to psychiatrists by primary care
in drab clothing and appearing somewhat ill at ease. Her chief
physicians. In the June 2002 Primary Care Sales Force Resource
complaint is, ‘I feel so anxious and irritable lately.’ Today, she says
Guide (), the prevalence of bipolar disorder is esti-
she’s been sleeping more than usual and has trouble concentrating
mated to be as high as 6%, an estimate much higher than epide-
at work and at home. However, several appointments earlier, she
miological lifetime prevalence estimates for bipolar I, which range
was talkative, elated, and reported little need for sleep.’’
from about 1% to 3%; only estimates that include ‘‘subthreshold’’
Under the heading ‘‘Create Action’’, a script read, ‘‘I would like
cases of bipolar disorder have found a 6% lifetime prevalence rate
you to get a patient like Donna started today. I will be back in
a week to follow up’’ (pg. 8). In another document,
Rather than limiting representatives to discussing clear-cut cases of
a more detailed description of Donna is provided. She was
bipolar I (for which olanzapine was FDA-indicated) olanzapine was
described as exhibiting the four ‘‘core symptoms [of complicated
instead marketed as a treatment for ‘‘complicated mood,’’ a cluster
mood, including] mood swings, irritability, sleep disturbances and
of symptoms that seems related to a notably less severe variety of
anxiety, as well as other symptoms including a lack of concentra-
bipolar disorder. For example, a script in the 2002 Primary Care
tion, mood lability and increased energy, depressed mood, loss of
Sales Force Resource Guide, stated: ‘‘Doctor, you treat patients who
interest, and agitation.’’ The symptoms were described as occurring
present with complicated mood symptoms. Many of these patients
simultaneously, ‘‘hence her mixed [i.e., mixed episode] presenta-
are struggling to gain control of symptoms like anxiety, irritability,
disruptive sleep, and mood swings.’’ , pg. 5). In
The hypothetical patient named Mark ‘‘is a middle-aged male
addition, a visual aid to be used by representatives’ lists anxiety,
brought in by his wife. He appears agitated and disheveled. His wife
irritability, disturbed sleep, and mood swings as the core compo-
says that he is irritable and causing problems at home but he
nents of complicated mood pg. 6). According to the
believes he is ﬁne.’’ It is further mentioned that he has had
DSM-IV, anxiety is not a symptom of bipolar disorder and it is
‘‘periods’’ where he needed little sleep and had ‘‘signiﬁcantly
unclear to what extent disturbed sleep maps onto the DSM-IV
increased energy.’’ Further, his ‘‘anger and mood swings are causing
criterion of decreased need for sleep for bipolar disorder. The use of
trouble at work’’ (, pg. 9). In another document, his
mood swings as a descriptor is likewise unclear, and it is likely that
symptoms were said to be indicative of a manic episode
many more people would endorse having ‘‘mood swings’’ than
would actually meet the DSM-IV criteria for shifting between
An undated document titled ‘‘PCP Discussion Guide,’’ focused on
clinically signiﬁcant episodes of mania and depression.
‘‘using olanzapine for patients with complicated mood symptoms.’’
The ‘‘complicated mood patient’’ was said to relate to ‘‘untapped
Three patients (Ashley, Andrea, and Cindy) were described. Ashley
growth potential’’ for the use of olanzapine in primary care settings
was described as having insomnia, irritability, distractibility,
, pg. 3). As touched on related above, under the ‘‘PCP
and racing thoughts. She also ‘‘has a tendency to be over-talkative.’’
Vision’’ of olanzapine, it was stated that the plan was to ‘‘expand our
, pg. 4). DSM-IV criteria for bipolar I disorder
market by redeﬁning how primary care physicians identify, diagnose,
require signiﬁcant impairment in social or occupational func-
and treat complicated mood disorders (i.e., bipolar disorder)
tioning, psychotic features, or hospitalization to prevent harm to
pg. 2).’’ In June 2002, it was written, regarding complicated
self or others; no such impairment is noted in Ashley’s case.
mood, ‘‘we’ve only scratched the surface of a market with tremendous
Andrea, another hypothetical case, was described as suffering
upside’’ (pg. 5). Sales representatives were instructed
from a variety of depressive symptoms. After taking an antide-
to handle primary care physician concerns that they do not treat
pressant for 10 days, her behavior became ‘‘increasingly irritable,
bipolar or schizophrenia as follows: ‘‘Make sure the PCP recognizes the
restless, anxious, hyperverbal, and [she] experiences great difﬁculty
type of patient we are talking about today, not the psychotic or
sleeping (pg. 7).’’ She was then labeled as manic and treated
severely ill patient, but the complicated mood patient who has
symptoms of irritability, anxiety, poor sleep and mood swings’’
The case named Cindy suffered from a variety of depressive
pg. 1). Such symptoms do not appear to meet DSM-IV
symptoms as well as distractibility, irritability, inability to sit still,
and racing thoughts. After taking an antidepressant, she became
A Lilly market researcher suggested that bipolar disorder tends
‘‘very anxious, agitated and hyperactive, with pressured speech and
to lead primary care physicians to think of acutely manic patients,
racing thoughts (pg. 12).’’ After taking olanzapine, she ‘‘reports
‘‘less so the hypomanic or less severely ill patient, which tend to be
signiﬁcant improvement’’ within one week (pg. 12).
the patients presenting most often in their ofﬁces (
The scenarios of Cindy, Andrea, and Ashley were not discussed
pg. 3).’’ The same market researcher suggested that sales repre-
directly in further documents, though one document (
sentatives ‘‘help [primary care physicians] recognize the ‘mushy
) referred to ‘‘three good complicated mood case summa-
middle’ patients they are already treating. pg. 7).’’ It
ries’’, (pg. 2). It may well be that this is a reference to the afore-
was also suggested that patients on ‘‘the low to middle end’’ of
mentioned three cases as it also mentioned an email attachment
bipolar severity, who were ‘‘higher functioning’’ receive olanzapine
partially titled ‘‘PCP DiscGd’’, which coincides with the document
treatment via their primary care physicians , pg. 11).
titled ‘‘PCP Discussion Guide’’ (that described
G.I. Spielmans / Social Science & Medicine 69 (2009) 14–20
the three cases. The ‘‘PCP Discussion Guide’’ further stated that ‘‘I
disturbances without impairing her cognitive functioning (
would highly suggest we direct reps to utilize’’ the three cases in
marketing (pg. 1). However, it is unclear to what extent these cases
The script went on to ask, ‘‘Do you see patients like Martha?
were utilized to promote olanzapine in the primary care setting.
What medication(s) do you prescribe in treating her behavioral
Another mood-related patient proﬁle, Michael, was included in
a document titled ‘‘Olanzapine Primary Care Q3 Implementation
According to a media report a Lilly spokes-
Guide’’, dated June 2001 (). Michael was described as
person indicated that the Martha proﬁle was utilized to reference
‘‘highly functional’’ but ‘‘prone to mood swings’’ and as having
a patient with untreated schizophrenia; however, Martha’s case
switched from ‘‘down, unmotivated, detached’’ to ‘‘wired, irritable,
seems more consistent with mild dementia rather than schizo-
and anxious.hasn’t been sleeping much.’’ His wife was concerned
phrenia that has remained undetected for decades. Olanzapine is
about his ‘‘recent spending habits and erratic behavior’’ (pg. 12).
typically utilized in doses of at least 10–15 mg daily for schizo-
In addition, one other patient proﬁle, David, was described very
brieﬂy in one document. Though it appears that David represented
a patient with bipolar disorder, he was later replaced by Michael,
suggested that patients like Martha receive doses in the 2.5 mg–
perhaps because market research ) labeled David as
5 mg range (a range typical of what was utilized in
a ‘‘strike out’’ pg. 8). Based upon the description of
their symptoms, the cases described above do not appear to
reference clear-cut cases of bipolar I disorder.
although Lilly claimed that they intended Martha’s proﬁle torepresent a patient with schizophrenia, an internal email stated
that the diagnosis of Martha was ‘‘dementia’’ (pg. 1),followed by a comment that ‘‘we are getting a little grief from some
As early as 1996, Lilly sought to collect data for an FDA indication
of our docs about promoting Zyprexa for dementia’’ (pg. 1). Several
for ‘‘psychosis in Alzheimer’s’’ pg. 43) and, in
psychiatrists have disagreed with the assessment of Martha’s case
a Zyprexa Product Team document from 1997, ‘‘dementia with
as one of schizophrenia, noting that schizophrenia ‘‘could not be
psychosis’’ was listed in the highest priority group for olanzapine
confused with mild dementia’’ ).
under ‘‘disease state prioritization’’ (pg. 18). In 1999,a document that focused on primary care physicians stated that
‘‘Dementia should be ﬁrst message’’ , pg. 1); the samedocument added that some physicians ‘‘might prescribe outside of
It is likely that few primary care physicians treat schizophrenia
label’’ (pg. 2). Further, in 2001, the Integrated Product Plan for
on a regular basis. However, the primary care marketing campaign
olanzapine stated that the drug would remain the ‘‘bestselling
placed signiﬁcant emphasis on symptoms of ‘‘thought distur-
psychotropic drug in history’’ by treating people suffering from
bances,’’ including discussion of disorganized thinking, as well as
‘‘schizophrenia, bipolar disorder, and dementia’’
poor attention, poor judgment and lack of insight
pg. 5). Documents provided various timelines for expected FDA
Olanzapine was speciﬁcally marketed for ‘‘mood,
approval in dementia, though olanzapine never received FDA
thought, and behavior disorders’’ in an ‘‘intentionally broad and
approval for the population with dementia (
vague’’ manner, ‘‘providing latitude to frame the discussion around
). Lilly appears to have stopped pursuing FDA approval
symptoms and behaviors rather than speciﬁc indications’’
pg. 1). While schizophrenia is not treated frequently by
zapine carries a label warning (along with other atypical antipsy-
PCPs, one document mentioned the idea of treating schizophrenia
chotics) that the drug is related to an increased risk of death when
or ‘‘schizophrenia lite’’ in primary care (pg. 7).
taken by elderly patients with dementia-related psychoses.
Zyprexa brand manager, Mike Bandick stated that donepezil
(a cholinesterase inhibitor popularly used in dementia) belongs toa ‘‘companion’’ class of medication, a drug ‘‘we augment rather
The proﬁle named Kelly was purportedly designed to represent
than replace’’ pg. 23). Further, it is mentioned
a patient with some form of psychotic disorder. Kelly was described
that the marketing of olanzapine in long-term care settings
as becoming more ‘‘socially isolated and fearful. Her personal
(where dementia is quite common) may have adversely impacted
hygiene is starting to decline and she is difﬁcult to draw out.[her
olanzapine sales in bipolar and schizophrenia markets (
family says] ‘she thinks people are talking about her behind her
back’’’. The description of Kelly does not appear to place her intoany recognized DSM-IV disorder category. She is described earlier
in the document as struggling with ‘‘mild to moderate psychosis.’’
In a manner similar to bipolar disorder/complicated mood,
Kelly replaced a proﬁle named Christine (that was
documents detailed the marketing of dementia to primary care
listed as a patient with ‘‘schizophrenia lite’’ (A
physicians through the use of a hypothetical patient proﬁle,
detailed description of Christine was not located in the archive.
Kelly’s case replaced that of Christine because Kelly seemed ‘‘more
Martha is a widow who lives independently and has been your
treatable’’ in a primary care setting, while Christine seemed
patient for some time. She is becoming more complicated to
manage, and you note increasing agitation. Her sleep isdisturbed; she dozes during the day and is up most of the
night. Her family has shared their concerns with you, saying‘‘She thinks we’re trying to take advantage of her.’’ Martha’s
Starting in 2000, a sizable campaign was launched to increase
family doesn’t want to send her to a nursing home, but her
olanzapine prescriptions in primary care. Materials utilized by sales
agitation and confusion must be addressed. Your goals of
representatives in primary care contained a high prevalence esti-
treatment for Martha may include reducing her behavioral
mate for bipolar I disorder, as one document suggested that the
G.I. Spielmans / Social Science & Medicine 69 (2009) 14–20
prevalence of bipolar disorder was 6% (), yet the
It appears that olanzapine’s marketing in primary care can be
prevalence for bipolar I disorder has been estimated as much less
viewed as a similar attempt to market a drug for a new niche – ‘‘Just
as Prozac revolutionized the treatment of depression in the late 80s
In addition, as suggested above, hypothetical cases used
and throughout the 90s, so too will Zyprexa forever change the way
various diagnostic criteria that were overly inclusive, and presented
primary care physicians view and treat bipolar disorder’’
scenarios of several patients who did not seem to meet criteria for
, pg. 3). Carving out new niches and expanding a drug’s uses to
bipolar I disorder or schizophrenia. Based upon review of several
a wide range of medical conditions (deﬁned loosely) is a common
documents, it appears that sales representatives were instructed to
tactic. In a pharmaceutical trade publication, it was written that
market olanzapine as a treatment for patients well outside of its
‘‘indication expansion is also tried and tested in the psychotropic
ﬁeld, where diagnostic distinctions can be blurred.(,
In addition, there is evidence that Lilly
para. 22).’’ The expansion of somewhat fuzzy boundaries of mental
promoted olanzapine off-label for dementia
illness makes perfect sense in a highly competitive market in which
), and marketed olanzapine as a long-term
various pharmaceutical companies are attempting to maximize
treatment for bipolar disorder in advance of its FDA approval for the
sales. Such expanded deﬁnitions open the gates to more people
qualifying as mentally ill, for which they might receive treatment
The relatively mild symptoms marketed by Lilly as components of
with ‘‘broad spectrum psychotropics’’ that purportedly work to
‘‘complicated mood’’ (anxiety, irritability, disturbed sleep, and mood
alleviate a wide variety of symptoms. Part of such market expansion
swings) are ill-deﬁned and, to some extent, are likely to be experi-
occurs by marketing to primary care physicians, who have access to
enced by a large number of people. Labeling this constellation of ill-
a wide base of patients. Indeed, it is interesting to note that Lilly’s
deﬁned and likely common symptoms as indicative of a mental
most famous product, ﬂuoxetine (Prozac), was successful largely
condition is suggestive of ‘disease mongering’ a term referencing the
because it vastly expanded the depression treatment market into
effort of pharmaceutical companies to broaden the market by
convincing patients (and physicians) that a large number of people
As described in the paper and elsewhere (e.g.,
are suffering from a (usually relatively mild) illness which would
beneﬁt from pharmaceutical intervention (
companies utilize many methods to market their products. It is not
In trade journals, pharmaceutical industry insiders have
entirely clear why patient proﬁles were seemingly utilized quite
plainly stated that expanding the market for their products via
frequently in the marketing of olanzapine in primary care, though
‘‘condition branding’’ (an industry term analogous to ‘disease
one document pointed out that the proﬁles would aid physicians in
mongering’) is a highly useful tool in the marketing arsenal
recognizing symptoms and in ‘‘early identiﬁcation of relevant
). Indeed, the current corpus of internal
documents hints that, in addition to marketing olanzapine, sales
Given that olanzapine was estimated to hit over $350 million in
representatives were also marketing the expanded boundaries of
primary care sales in 2003, it appears that a reasonably large
bipolar disorder. No longer was bipolar disorder a relatively
number of patients in primary care received olanzapine prescrip-
uncommon condition relegated to treatment by psychiatrists, it was
tions. As the primary care marketing campaign seemed focused
to be marketed as a common illness with a broad spectrum of severity
primarily on cases suffering from relatively mild mental distress
that warranted treatment in primary care. Despite an expanded
(e.g., ‘‘complicated mood’’), many patients who were prescribed
treatment market, there is a paucity of controlled clinical trial data
olanzapine via primary care may have been prescribed treatment
regarding the beneﬁts and risks of treating adults with mild symp-
that lacked a supporting evidence base. Several studies have linked
toms of bipolar disorder/complicated mood with ‘mood stabilizers’ or
atypical antipsychotics such as olanzapine
One document stated that Lilly was committed to position
olanzapine as a ‘‘broad spectrum psychotropic to differentiate it
from other antipsychotics.’’ (). Such a focus on
may increase risk for cardiovascular disease
product differentiation is sensible in a crowded marketplace of
Indeed, the olanzapine label was updated in October 2007 to
atypical antipsychotic medications. Indeed, product differentiation
reﬂect an increased risk of hyperglycemia, hyperlipidemia, and
is a key component of modern-day marketing, with products from
weight gain. Thus, it is quite possible that some patients received
cola to toilet cleaners to antidepressants marketed on the basis of
a treatment of questionable efﬁcacy that resulted in adverse health
their ostensible uniqueness, often in spite of their high degree of
effects, though the current documents do not clarify to what extent
similarity to competing products (Lilly also
such health consequences may have occurred.
emphasized product differentiation when marketing its antide-
This study has a number of limitations, the most obvious of
pressant duloxetine as a treatment for patients with depression
which is the reliance on the present set of documents. Though their
who also suffer from physical pain, as research indicated that
authenticity has not been challenged, it is certainly possible that
entering this niche market would differentiate duloxetine from its
the documents may have been taken out of context and that further
competition As part of the marketing strategy for
internal documents related to olanzapine’s promotion would paint
duloxetine, hypothetical patient proﬁles tailored to the perceived
a different picture of how the drug was marketed. However, this
market were created, though it is unclear to what extent the patient
seems unlikely given that the documents obtained were quite
proﬁles were used in detailing visits (This niche
consistent in their descriptions of the marketing of the compound.
strategy appears to have been successful, as duloxetine sales
The documents were reviewed by one author, so it is possible that
exceeded $2 billion in 2007. Indeed, Lilly expects duloxetine sales to
different reviewers may come to different conclusions. As all the
overtake those of its current bestseller, olanzapine, in 2008
internal documents are accessible by the public online
(Despite the successful marketing of duloxetine,
they can be easily examined by anyone who
a recent meta-analysis concluded that the drug yielded little to no
wishes to check the veracity of the current author’s claims. The source
beneﬁt over placebo in treating pain symptoms in depression
material was also somewhat dated, in that documents reviewed
(though Lilly claims duloxetine is indeed effec-
dated from 1995 to 2004. Practices regarding the marketing of olan-
zapine that have occurred since 2004 are thus unknown.
G.I. Spielmans / Social Science & Medicine 69 (2009) 14–20
Given that regulations surrounding off-label marketing are
De Deyn, P. P., Carrasco, M. M., Deberdt, W., Jeandel, C., Hay, D. P., Feldman, P. D., et
al. (2004). Olanzapine versus placebo in the treatment of psychosis with orwithout associated behavioral disturbances in patients with Alzheimer’s
disease. International Journal of Geriatric Psychiatry, 19, 115–126.
is not an attorney, this paper makes no claims as to the legality of
Demer, L. (February 14, 2007). Anchorage attorney ordered to return documents on
any of the practices utilized in the promotion of olanzapine.
drug; Zyprexa: judge says publicized papers meant to be sealed were stolen.Anchorage Daily News B2.
The current examination of Lilly’s marketing of olanzapine in
Dobbs, D. (2000). Email correspondence (subject: Zyprexa questions from the ﬁeld).
primary care adds to a small but burgeoning literature on the
intersection between pharmaceutical companies and the bound-
Eaton, M. L., & Xu, M. (2005). Developing and marketing a blockbuster drug: Lessons
from Eli Lilly’s experience with Prozac. Boston: Harvard Business School Press.
Eli Lilly. (1995). Zyprex – a major step toward a health care solution for psychosis.
should seek to examine the impact of such marketing tactics, taking
Eli Lilly. (1999). PCP-APS. Available from
ideas from guidelines offered previously
From a social science perspective, these internal industry
Eli Lilly. (2000). Zyprexa launch meeting. Available from
documents are a rare ﬁnd. Documents from the present archive
Eli Lilly. (2001a). Zyprexa product team off-site: July 25, 2001. Available from
detailing how Lilly handled issues with potential health concerns
related to olanzapine will likely be of interest to social scientists, as
the documents seem to involve a potentially interesting intersec-
Eli Lilly. (2001b). ZyprexaÒ (olanzapine) primary care Q3 implementation
tion of marketing, health, and public relations concerns.
A physician afﬁliated with the FDA wrote that regulation of off-
Eli Lilly. (2001c). Hyperglycemia/diabetes: sell sheet implementation. Available
label marketing in the pharmaceutical industry is needed in order
to prevent ‘‘harm to patients from unstudied uses that actually lead
to bad results, or that are merely ineffective’’ and that insufﬁciently
regulated off-label drug marketing ‘‘could ultimately erode the
Eli Lilly. (2001e). 2001 Integrated product plan: Zyprexa product team. Available
efﬁcacy standard’’ (pg. 6). In the wake of revela-
tions regarding olanzapine’s off-label marketing, it may behoove
regulatory agencies to attend more closely to such practices.
Eli Lilly. (2002a). Zyprexa US business plan – executive summary: Gerhard Mayr
review – October 17, 2002. Available from Accessed 15.02.07.
Eli Lilly. (2002b). Zyprexa primary care sales force resource guide. Available from
I sincerely thank Kalman Applbaum, David Healy, and three
Eli Lilly. (2002c). Zyprexa PCP moderator slides. Available from
anonymous reviewers for their helpful comments on prior versions
Eli Lilly. (2002d). Managed care – June 2002: information about ZyprexaÒ
of the manuscript. In addition, I acknowledge the careful review of
British attorneys in helping to shape the ﬁnal version of this article.
I also thank Philip Dawdy for hosting the documents which formed
Eli Lilly. (2002f). Zyprexa product team SMEC pre-read. Available from
Eli Lilly. (2003). Untitled. Available from
Angelmar, R., Angelmar, S., & Kane, S. (2007). Building strong condition brands.
Journal of Medical Marketing, 7, 341–351.
Anonymous. (2007). Zyprexa kills directory. Available from
Eli Lilly. (2009). Lilly resolves investigations of past Zyprexa marketing and
Antonuccio, D. O., Danton, W. G., & McClanahan, T. M. (2003). Psychology in the
prescription era: building a ﬁrewall between marketing and science. American
Eli Lilly (undated-a). Zyprexa complicated mood project. Available from
Applbaum, K. (2004). The marketing era. NY: Routledge.
Bandick, M. (2000a). Zyprexa – primary care strategy and implementation over-
Eli Lilly. (undated-b). Zyprexa ‘‘frequent areas of concern’’ or ‘‘FAOC’’ Available
Bandick, M. (2000b). Zyprexa primary care presentation. Available from
Eli Lilly. (undated-c). Patient/dosing clarity document. Available from
Berenson, A. (December 18, 2006). Drug ﬁles show maker promoted unapproved
Berenson, A. (January 4, 2007a). Mother wonders if psychosis drug helped kill son.
Eli Lilly. (undated-e). Zyprexa retail implementation guide. Available from
Berenson, A. (January 5, 2007b). U.S. wonders if drug data was accurate. New York
Gianfrancesco, F., Wang, R. H., & Nasrallah, H. A. (2006). The inﬂuence of study
Berenson, A. (January 20, 2007c). States study marketing of Lilly pill. New York
design on the results of pharmacoepidemiologic studies of diabetes risk with
antipsychotic therapy. Annals of Clinical Psychiatry, 18, 9–17.
Berenson, A. (October 6, 2008). 33 states to get $62 million in Zyprexa case
Glaser, B. G., & Strauss, A. L. (1967). The discovery of grounded theory. Chicago: Aldine.
Goldstein, B. (2007). How Lilly sells Zyprexa. Slate. Available from
Bogenschutz, M. P., & Nurnberg, H. G. (2004). Olanzapine versus placebo in the
treatment of borderline personality disorder. Journal of Clinical Psychiatry, 65,
Grant, B. F., Stinson, F. S., Hasin, D. S., Dawson, D. A., Chou, S. P., Ruan, W. J., et al.
(2005). Prevalence, correlates, and comorbidity of bipolar I disorder and
Crespo-Facorro, B., Perez-Iglesias, R., Ramirez-Bonilla, M., Martinez-Garcia, O.,
axis I and II disorders: results from the National Epidemiologic Survey on
Llorca, J., & Luis Vazquez-Barquero, J. (2006). A practical clinical trial comparing
Alcohol and related conditions. Journal of Clinical Psychiatry, 66, 1205–1215.
haloperidol, risperidone, and olanzapine for the acute treatment of ﬁrst-
Guo, J. J., Keck, P. E., Jr., Corey-Lisle, P. K., Li, H., Jiang, D., Jang, R., et al. (2006). Risk of
episode nonaffective psychosis. Journal of Clinical Psychiatry, 67, 1511–1521.
diabetes mellitus associated with atypical antipsychotic use among patients
with bipolar disorder: a retrospective, population-based, case–control study.
Journal of Clinical Psychiatry, 67, 1055–1061.
G.I. Spielmans / Social Science & Medicine 69 (2009) 14–20
Guo, J. J., Keck, P. E., Jr., Corey-Lisle, P. K., Li, H., Jiang, D., Jang, R., et al. (2007). Risk of
Ofek, E. (2007). Eli Lilly: Developing cymbalta. Boston: Harvard Business School Press.
diabetes mellitus associated with atypical antipsychotic use among Medicaid
O’Reilly, J., & Dalal, A. (2003). Off-label or out of bounds? Prescriber and marketer
patients with bipolar disorder: a nested case–control study. Pharmacotherapy,
liability for unapproved uses of FDA-approved drugs. Annals of Health Law, 12,
Hall, R. J., & Berlin, R. J. (2006). When you have a hammer everything looks like
Porat, Z. (2002). Research summary and recommendations ﬁrst quarter 2002:
a nail: misapplication of the False Claims Act to off-label promotion. Food and
zyprexa in primary care. Available from.
Healy, D. (2004). Let them eat Prozac. NY: New York University Press.
Robinson, D. G., Woerner, M. G., Napolitano, B., Patel, R. C., Sevy, S. M., Gunduz-
Healy, D. (2006). The latest mania: selling bipolar disorder. PLoS Medicine, 3,
Bruce, H., et al. (2006). Randomized comparison of olanzapine versus risper-
idone for the treatment of ﬁrst-episode schizophrenia: 4-month outcomes.
Hisey, T. (2004). The big squeeze. Pharmaceutical Executive, 24, 86–98, Available
American Journal of Psychiatry, 163, 2096–2102.
Schneider, L. S., Dagerman, K., & Insel, P. S. (2006). Efﬁcacy and adverse effects of
atypical antipsychotics for dementia: meta-analysis of randomized, placebo-
Hobson, V. A. (2001). Email correspondence (subject: Dr. Leming letter). Available
controlled trials. American Journal of Geriatric Psychiatry, 14, 191–210.
Schneider, L. S., Tariot, P. N., Dagerman, K. S., Davis, S. M., Hsiao, J. K., Ismail, M. S., et
al., , CATIE-AD Study Group. (2006). Effectiveness of atypical antipsychotic
IMS Health. (2000). Leading products by global sales. Accessed 04.05.07.
drugs in patients with Alzheimer’s disease. New England Journal of Medicine,
IMS Health. (2001). Leading products by global pharmaceutical sales. Accessed
Siegel, M. (December 25, 2006). Pressured to prescribe: the drug rep was only too
IMS Health. (2002). Leading products by global pharmaceutical sales. Accessed
happy to ﬁll his sample closet with an antipsychotic. Los Angeles Times F3.
Silverman, E. (2008). Overstated claims hurt: cymbalta ad is skewered. Available
IMS Health. (2003). Leading products by global pharmaceutical sales. Accessed
IMS Health. (2004). Leading products by global pharmaceutical sales. Accessed
Spielmans, G. I. (2008). Duloxetine does not relieve painful physical symptoms in
depression: a meta-analysis. Psychotherapy and Psychosomatics, 77, 12–16.
I.M.S.Health. (2005). Accessed 04.05.07.
Steinman, M. A., Bero, L. A., Chren, M. M., & Landefeld, C. S. (2006). Narrative review:
the promotion of gabapentin: an analysis of internal industry documents.
Annals of Internal Medicine, 145, 284–293.
Strassnig, M., Miewald, J., Keshavan, M., & Ganguli, R. (2007). Weight gain in newly
IMS Health. (2007). Top ten global products. Available from
diagnosed ﬁrst-episode psychosis patients and healthy comparisons: one- year
analysis. Schizophrenia Research, 93, 90–98.
Takahashi, H., Kamata, M., Yoshida, K., Ishigooka, J., & Higuchi, H. (2006). Switching
Judd, L. L., & Akiskal, H. S. (2003). The prevalence and disability of bipolar
to olanzapine after unsuccessful treatment with risperidone during the ﬁrst
spectrum disorders in the US population: re-analysis of the ECA database
episode of schizophrenia: an open-label trial. Journal of Clinical Psychiatry, 67,
taking into account subthreshold cases. Journal of Affective Disorders, 73,
Thase, M. E., Corya, S. A., Osuntokun, O., Case, M., Henley, D. B., Sanger, T. M., et al.
Kahan, J. S., & Shapiro, J. K. (2003). The ﬁrst amendment and the food and drug
(2007). A randomized, double-blind comparison of olanzapine/ﬂuoxetine
administration’s regulation of labeling and advertising: three proposed reforms.
combination, olanzapine, and ﬂuoxetine in treatment- resistant major depres-
Food and Drug Law Journal, 58, 353–364.
sive disorder. Journal of Clinical Psychiatry, 68, 224–236.
Kinon, B. J., Noordsy, D. L., Liu-Seifert, H., Gulliver, A. H., Ascher-Svanum, H., &
Tollefson, G. D. (1997). Zyprexa product team 4-column summary. Available from
Kollack-Walker, S. (2006). Randomized, double-blind 6-month comparison of
olanzapine and quetiapine in patients with schizophrenia or schizoaffective
disorder with prominent negative symptoms and poor functioning. Journal of
United States Department of Justice. (January 15, 2009). Eli Lilly and company
Clinical Psychopharmacology, 26, 453–461.
agrees to pay $1.415 billion to resolve allegations of off-label promotion of
Lambert, B. L., Cunningham, F. E., Miller, D. R., Dalack, G. W., & Hur, K. (2006).
Diabetes risk associated with use of olanzapine, quetiapine, and risperidone in
veterans health administration patients with schizophrenia. American Journal of
Weissman, M. M., Bland, R. C., Canino, G. J., Faravelli, C., Greenwald, S., Hwu, H. G., et
al. (1996). Cross-national epidemiology of major depression and bipolar
Lopatto, E. (2008). Eli Lillys fourth-quarter proﬁt gains on cymbalta. Bloomberg News.
Woloshin, S., & Schwartz, L. M. (2006). Giving legs to restless legs syndrome. PLoS
Moynihan, R., & Cassels, A. (2005). Selling sickness. Nation Books.
Woodcock, J. (1997). A shift in the regulatory approach. Available from.
Moynihan, R., & Henry, D. (2006). The ﬁght against disease mongering: generating
knowledge for action. PLoS Medicine, 3, e191.
Newcomer, J. W., & Haupt, D. W. (2006). The metabolic effects of antipsychotic
Zyprexa Litigation, et al. (2007). 07-CV-0504 (E.D. NY 2007). Available from.
medications. Canadian Journal of Psychiatry, 51, 480–491.

Pneumonia Pneumonia is a respiratory condition in which there is inflammation of the lung. Community-acquired pneumonia refers to pneumonia in people who have not recently been in the hospital or another health care facility (nursing home, rehabilitation facility). Pneumonia is a common illness that affects millions of people each year in the United States. Germs called bacteria, viruses,